The Hylemon-Björkhem pathway of bile acid 7-dehydroxylation: history, biochemistry, and microbiology

Bile acids are detergents derived from cholesterol that function to solubilize dietary lipids, remove cholesterol from the body, and act as nutrient signaling molecules in numerous tissues with functions in the liver and gut being the best understood. Studies in the early 20th century established the structures of bile acids, and by mid-century, the application of gnotobiology to bile acids allowed differentiation of host-derived primary bile acids from secondary bile acids generated by host-associated microbiota. In 1960, radiolabeling studies in rodent models led to determination of the stereochemistry of the bile acid 7-dehydration reaction. A two-step mechanism was proposed, which we have termed the Samuels-son-Bergstrom model, to explain the formation of deoxycholic acid. Subsequent studies with humans, rodents, and cell extracts of Clostridium scindens VPI 12708 led to the realization that bile acid 7-dehydroxylation is a result of a multi-step, bifurcating pathway that we have named the Hylemon-Bjorkhem pathway. Due to the importance of hydrophobic secondary bile acids and the increasing measurement of microbial bai genes encoding the enzymes that produce them in stool metagenome studies, it is important to understand their origin.

Automated summary

Bile acids are derived from cholesterol and function as detergents to solubilize lipids and remove cholesterol. They also act as signaling molecules in various tissues. The structures of bile acids were established in the early 20th century, and research has since differentiated primary from secondary bile acids. The formation of bile acids involves a multi-step, bifurcating pathway.